Positron Emission Tomography (PET) is a molecular imaging modality that utilizes radiolabeled molecules (probes) to target and measure biological processes. Basic scientists can use the same probes to examine microorganisms, cells, and mice as they do in patients to visualize and characterize the biology of disease, monitor its progression, and evaluate therapeutic efficacy. Although over 1,600 PET probes have been developed to help answer a variety of biological questions, including many specific to understanding the structure and function of the human brain, only the glucose analog [18F]FDG is routinely used for molecular imaging diagnostics in patient care today. This limitation exists because of the centralized approach to PET probe production necessitated by the high cost of infrastructure, specialized equipment, and skilled personnel required for synthesis. Overcoming these hindrances to PET probe development, optimization, and routine production is necessary to facilitate the entry of numerous other promising PET probes into clinical research and trials, and to select those with value as companion biomarkers. A decentralized approach to PET probe development is required to give scientists the freedom to determine what probes they want to use to best solve the problems of their interest. This goal can be achieved by building a benchtop, PC-controlled, microfluidic chip-based commercial device for the on-demand production of PET probes. Phase I of this project will answer basic commercial feasibility questions about the underlying Electro- Wetting-On-Dielectric (EWOD) microfluidic chip technology. In Aim 1, we will develop a reagent loading system for a radiochemistry-based EWOD device that will enable full automation of on-chip syntheses for increased usability and safety. In Aim 2, we will demonstrate that the EWOD platform is capable of diverse syntheses by preparing additional PET compounds beyond the [18F]FDG proof-of-concept studies to date. The focus will be on compounds specifically relevant to brain imaging. Phase II will produce a commercial prototype of the device, complete with a PC-based control system that contains an inexpensive, disposable, probe-specific cartridge of the microfluidic chip and associated reagents. As an eventual product, a library of chips will be developed based on customer needs for different probes. Shifting to a point-of-research/point-of-care model is a transformational solution that removes the limitations imposed by the centralized model on probe production, cost, and diversity. By empowering scientists and clinicians to control the development and use of PET probes, they are able to focus on processes that they believe are most important. PUBLIC HEALTH RELEVANCE: Novel molecular imaging modalities to measure biochemical and cellular events in patients are needed in personalized medicine to transform the care of patients with brain disorders. The goal of this proposal is to develop an affordable, compact, chip-based device to produce PET probes, thereby enabling scientists to image diverse biological systems by eliminating barriers that currently limit probe availability and diversity. The scientific yield from this may lead to improved therapies for the pathophysiology of brain disorders, significantly affecting public health.